氟喹诺酮类药物临床使用往往伴随血糖紊乱不良反应。肠道胆汁酸分别通过G蛋白偶联受体(TGR5)或法尼醇X受体(FXR)促进或抑制胰高血糖素样肽-1(GLP-1)释放，不同胆汁酸成分对TGR5和FXR作用是不同的。氟喹诺酮药物属于抗菌药，同时影响一些肠道转运体功能。前期研究显示氟喹诺酮药物也影响GLP-1分泌，该过程与TGR5有关，提示肠道胆汁酸代谢紊乱可能是氟喹诺酮药物诱发血糖紊乱主要原因之一。本项目以环丙沙星为代表，从在体和细胞两个层面研究环丙沙星引起肠道胆汁酸组成改变及其对GLP-1分泌的影响，以及与TGR5和FXR的关系。围绕影响肠道胆汁酸组成的关键因素，肠道菌群和胆汁酸肠肝循环，分析环丙沙星干预后肠道菌群分布与肠道胆汁酸谱改变的相关性以及环丙沙星对肠道胆汁酸吸收和胆汁酸胆汁排泄影响。其研究成果有助于揭示氟喹诺酮药物引起血糖紊乱机制，对该类药物临床合理使用和不良反应预测具有重要意义。

A variety of fluoroquinolone agents have been reported to cause dysglycemia. Intestinal bile acids act as signaling molecules via G protein-coupled receptor TGR5 and the nuclear receptor FXR to stimulate or inhibit glucagon-like peptide 1(GLP-1) secretion and regulate glucose homeostasis. Different bile acids exert different effects on TGR5 and FXR. Fluoroquinolone agents are antibacterial drug which may also affect the function and expression of some transporters in intestinal tract. Our previous studies proved the stimulation effect of fluoroquinolone agents on GLP-1 secretion and showed that TGR5 pathway was involved, which indicated that disturbance of intestinal bile acids metabolism be one of the important mechanisms of fluoroquinolone-induced dysglycemia. Ciprofloxacin is served as a representative drug in this research. The effect of ciprofloxacin-induced changes of intestinal bile acids composition on GLP-1 secretion and the relation with TGR5 and FXR will be investigated. Gut microbiota and enterohepatic circulation of bile acids are two main mechanisms for changes of intestinal bile acids composition. Therefore the relation between ciprofloxacin-induced changes of gut microbiota and intestinal bile acid pool will be further studied. Besides, bile acids absorption and bile excretion will also be investigated to explore the effect of ciprofloxacin on enterohepatic circulation of bile acids. Our findings have important implications for understanding the mechanism of fluoroquinolones-induced dysglycemia, as well as providing guidance for rational use of fluoroquinolones and prediction of drug adverse effects.